The COVID-19 pandemic has strained hospital capacity and led to shortages in personal protective equipment and testing supplies. This is particularly concerning because the SARS-CoV-2 virus that causes COVID-19 has resulted in notable healthcare associated outbreaks, as have other novel coronaviruses such as SARS and MERS. Past studies have shown that these outbreaks are preventable with prompt diagnosis of cases and appropriate use of personal protective equipment. In the face of shortages, hospitals must make rapid decisions on strategies to room patients, assign infection control precautions, ration personal protective equipment, and maintain adequate staffing. Accurate data and projections are needed to inform these decisions and evaluating their success is critical to managing the ongoing outbreak and informing future response. This need can be met by applying the existing aims of K01AI141579 to hospital-associated SARS- CoV-2 infection. The overall objective of the existing K01 project is to support Josh Petrie, PhD in the development of expertise in healthcare epidemiology, state-of-the-art molecular methods, and advanced modeling techniques. Completion of this objective is in progress through focused training and career development activities in healthcare epidemiology, next generation sequencing, bioinformatics, cost- effectiveness analysis, and mathematical modeling that is overseen by an excellent team of mentors. The skills that are being developed by the training and career development objectives are strengthened by mentored research to accomplish the following Specific Aims: (1) Define the epidemiology and burden of community- acquired and hospital-associated respiratory virus infections and compare clinical impact by viral species; (2) Improve the sensitivity and specificity of case definitions to identify hospital-associated respiratory virus cases by integrating clinical, epidemiologic, and molecular data; and (3) Determine the cost-effectiveness of increased respiratory virus screening and expanded infection control measures to reduce HA-RVI using mathematical models. The proposed administrative supplement will facilitate application of these aims to hospital-associated SARS-CoV-2 infection. The expected research outcomes of the proposed project are, 1) determination of the incidence and outcomes of hospital-associated SARS-CoV-2 infections; 2) improved identification of hospital-associated SARS-CoV-2 infections through integration of clinical, epidemiologic, and molecular data; and 3) quantification of the effects of COVID-19 response strategies in the hospital on the incidence of hospital-associated SARS-CoV-2. The proposed research is significant because it is expected that the outcomes of this work and future studies that build upon it, will inform ongoing response to the COVID-19 pandemic and future pandemics. This research is innovative both in its use of cross-disciplinary methodology that allows for new avenues of research.